title: Regenerative toxicology: the role of stem cells in the development of chronic toxicities.
abstract: BACKGROUND
  Human stem cell lines and their derivatives, as alternatives to the use of animal cells or cancer cell lines, have been widely discussed as cellular models in predictive toxicology. However, the role of stem cells in the development of long-term toxicities and carcinogenesis has not received great attention so far, despite growing evidence indicating the relationship of stem cell damage to adverse effects later in life. However, testing this in vitro is a scientific/technical challenge in particular due to the complex interplay of factors existing under physiological conditions. Current major research programs in stem cell toxicity are not aiming to demonstrate that stem cells can be targeted by toxicants. Therefore, this knowledge gap needs to be addressed in additional research activities developing technical solutions and defining appropriate experimental designs.
  
  
  METHODS
  The current review describes selected examples of the role of stem cells in the development of long-term toxicities in the brain, heart or liver and in the development of cancer.
  
  
  CONCLUSIONS
  The presented examples illustrate the need to analyze the contribution of stem cells to chronic toxicity in order to make a final conclusion whether stem cell toxicities are an underestimated risk in mechanism-based safety assessments. This requires the development of predictive in vitro models allowing the assessment of adverse effects to stem cells on chronic toxicity and carcinogenicity.
authors.affiliation: Institute for Health and Consumer Protection, DG Joint Research Centre (JRC), European Commission, Systems Toxicology Unit , Via E. Fermi 2749, TP 580, 21027 Ispra (VA) , Italy +39 0332 785914 ; +39 0332 785336 ; susanne.bremer@jrc.ec.europa.eu.
authors.forename: David
authors.initials: D
authors.lastname: Canovas-Jorda
authors.forename: Jochem
authors.initials: J
authors.lastname: Louisse
authors.forename: Francesca
authors.initials: F
authors.lastname: Pistollato
authors.forename: Dimitra
authors.initials: D
authors.lastname: Zagoura
authors.forename: Susanne
authors.initials: S
authors.lastname: Bremer
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced / Q000473:pathology; D013234:Stem Cells / Q000187:drug effects* / Q000473:pathology*; D036401:Toxicity Tests, Chronic / Q000379:methods*
chemical_list: D002273:Carcinogens